Origin of blood cells Flashcards
What is haematopoiesis
the commitment and differentiation processes that lead to the formation of all blood cells from haematopoietic stem cells
What is the stem cell lineage
- Stem cells
- Early progenitors
- Late progenitors
- Immature precursors
- Mature cells
What are key rules when it comes to stem cell lineage
The mature cells cannot go back to being stem cells
Only stem cells can divide to produce more stem cells
Progenitor cells are differentiated from stem cells but this cannot be seen through a microscope
Where does haematopoiesis occur in an early embryo
The yolk sac
Where does haematopoiesis occur in a foetus
The foetal liver
Where does haematopoiesis occur in an infant
Through the bone marrow
Where does haematopoiesis occur in an adult
The central skeleton (vertebrae, ribs and sternum, skull, sacrum, pelvis and the proximal end of the humerus and femur)
Whats red marrow
Active haematopoiesis
What yellow marrow
Filled with fat cells
What does a blood marrow trephine do and how is it performed
Its used to examine bone marrow architecture
remove a 1 or 2cm core of bone marrow in one piece
What is a bone marrow aspiration
sucks some bone marrow cells up into a syringe
What is the neutrophil lineage - myelopoiesis
- Myeloblast
- Promyelocyte
- Myelocyte
- Metamyelocyte
- Band
- Segmented neutrophil
What is the red blood cell lineage - erythropoiesis
- Pro-erythroblast
- Basophilic erythroblast
- Polychromatic erythroblast
- Pyknotic erythroblast
- Reticulocyte
- Mature red blood cell
Platelet formation
- Megakaryoblast - DNA replication but no cell division
- Megakaryocyte - Large, polypoid cell
- Blood platelets - cytoplasmic fragments
Lymphopoiesis
- Stem cell
- Common lymphoid progenitor
- T-lymphocytes and B-lymphocytes
T-cell formation in thymus
- Early progenitor migrates to thymus
- T-cell receptor gene rearrangement to get necessary antibodies
- Positive and negative selection to prevent auto immunity
B-cell formation in bone marrow
- immunoglobin gene rearrangment
- Expression of surface IgM
- Immature B-cell migrates to secondary lymphoid organs for maturation and antigen selection
How are progenitors undifferentiated
You cannot tell the difference between them morphologically because they do not show the characteristics of mature cells
How are progenitors committed
They are already committed as to what they will become when they generate mature cells
How do you form colonies
- Semi-solid medium
- Plus growth factors
- Single cell suspension of bone marrow
- Will form colonies
What colonies will progenitors form
Colonies of mature cells
Thus progenitors are called ‘colony forming units’ (CFU)
What colonies will early erythroid progenitors form
They will form ‘burst forming unit - erythroid’ (BFU-E)
What are CSF
Colony stimulating factors
How is a bone marrow transplant done
- Completely ablate haemopoiesis with radiation and drugs
- Infuse compatible donor bone marrow cells
- Haemopoiesis can be completely restored
What must bone marrow donors be
Must be HLA matched; sibling or unrelated donor
Or autologous BMT; Re-infuse patients own bone marrow
What are the applications of bone marrow transplant
- Leukaemia, lymphoma and myeloma
- Intensified chemotherapy
- Genetic diseases e.g. SCID, thalassaemia
What are the risks of a bone marrow transplant
- Significant mortality whilst waiting for engraftment
- Infection due to neutropenia (low neutrophil count)
- Bleeding
- Graft versus host disease (GVHD)
What are the benefits of of a bone marrow transplant
For many diseases this is the only curative treatment
How can stem cells be studied through mice
- Mark stem cells by retrovirus insertion
- Transplant irradiated mice with small number of stem cells
- Same marked stem cells gives rise to neutrophils and lymphocytes
How can stem cells be studied through humans
- Chronic myeloid leukaemia (CML) is caused by a chromosome translocation in stem cells
- provides a natural marker within cells
- The disease mostly effects neutrophil lineage, but Philadelphia chromosome also found in T-lymphocytes and other lineages
What are growth factors and how do they work
Polypeptide growth factors
Bind to cell surface transmembrane receptors
Stimulates growth and survival of progenitors
Where and why is erythropoietin produced and what does it do
Produced in the kidney is response to hypoxia
Increases red blood cell production by increasing survival of erythroid progenitors (CFU-E)
What is the clinical application of recombinant erythropoietin
Treating anaemia of kidney failure, alternative to blood transfusion in Jehovahs witnesses
Where is granulocyte colony stimulating factor (G-CSF) produced, why and what does it do
Produced by many cell types in response to inflammation
Its a glycoprotein that stimulates the bone marrow to produce neutrophils and neutrophil progenitors and release them into the bloodstream
What are the clinical applications of G-CSF
Stimulate neutrophil recovery after bone marrow transplantation and chemotherapy
Treatment of neutropenia
Treatment is seemed to be working after appearance of CD34
